02522nas a2200217 4500008004100000245019900041210006900240260001900309300001400328490000700342520175500349653002402104653002202128653000902150653002002159653003102179100003302210700000502243700002002248856003602268 2021 eng d00aIn Silico Analysis of Pinostrobin Derivatives from Boesenbergia pandurata on ErbB4 Kinase Target and QSPR Linear Models to Predict Drug Clearance for Searching Anti-Breast Cancer Drug Candidates0 aIn Silico Analysis of Pinostrobin Derivatives from Boesenbergia  cSeptember 2021 a1143-11490 v133 a

Background: ErbB4 is a member of ErbB family of receptor tyrosine kinases (RTKs) and plays an important role in resistance to ErbB2 inhibitors. Objective: This study aimed to design a pinostrobin derivative with activity as an ErbB4 inhibitor and to establish a quantitative structure-property relationship (QSPR) of pinostrobin and its derivatives to predict drug clearance. Materials and Methods: In this research, an in silico study was conducted on pinostrobin and its derivatives by predicting the prediction of activity spectra for substances (PASS) with PASS online, followed by molecular docking using the AutoDockTools 4.2.6 program on ErbB4 protein kinase and visualizing the docking results using the Discovery Studio Visualizer software. While the study of QSPR pinostrobin and its derivatives was determined using physicochemical parameters with clearance (CLtot) using SPSS. Results: From the data obtained, 5-O-2- phenylacetylpinostrobin has a high affinity for ErbB4 protein with a free energy of binding (ΔG) -10.37 kcal/mol and an inhibition constant (Ki) of 26.06 nM. Conclusion: Probability “to be active” (Pa) 5-O-2- phenylacetylpinostrobin of 0.595 for kinase inhibitors and 0.666 for apoptosis agonists, thus becoming candidates for breast cancer drugs. The QSPR model can be used to predict the properties of molecules such as CLtot, this will be useful in the drug design process. The best QSPR regression equation for pinostrobin and its derivatives is Log (1/CLtot) = 0.705 Log S + 0.035 MR + 0.375. This equation can be used as a reference in predicting CLtot.

10a5-O-acylpinostrobin10aMolecular docking10aPASS10aPharmacokinetic10aPhysicochemical properties1 aPraditapuspa, Ersanda, Nurma1 a1 aWidiandani, Tri uhttps://phcogj.com/article/1643